Publications by authors named "Wu Hong"

1,548 Publications

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Identification, systematic evolution and expression analyses of the AAAP gene family in Capsicum annuum.

BMC Genomics 2021 Jun 22;22(1):463. Epub 2021 Jun 22.

Biotechnology Research Center, Chongqing Academy of Agricultural Sciences/Chongqing Key Laboratory of Adversity Agriculture Research, Chongqing, 401329, China.

Background: The amino acid/auxin permease (AAAP) family represents a class of proteins that transport amino acids across cell membranes. Members of this family are widely distributed in different organisms and participate in processes such as growth and development and the stress response in plants. However, a systematic comprehensive analysis of AAAP genes of the pepper (Capsicum annuum) genome has not been reported.

Results: In this study, we performed systematic bioinformatics analyses to identify AAAP family genes in the C. annuum 'Zunla-1' genome to determine gene number, distribution, structure, duplications and expression patterns in different tissues and stress. A total of 53 CaAAAP genes were identified in the 'Zunla-1' pepper genome and could be divided into eight subgroups. Significant differences in gene structure and protein conserved domains were observed among the subgroups. In addition to CaGAT1, CaATL4, and CaVAAT1, the remaining CaAAAP genes were unevenly distributed on 11 of 12 chromosomes. In total, 33.96% (18/53) of the CaAAAP genes were a result of duplication events, including three pairs of genes due to segmental duplication and 12 tandem duplication events. Analyses of evolutionary patterns showed that segmental duplication of AAAPs in pepper occurred before tandem duplication. The expression profiling of the CaAAAP by transcriptomic data analysis showed distinct expression patterns in various tissues and response to different stress treatment, which further suggest that the function of CaAAAP genes has been differentiated.

Conclusions: This study of CaAAAP genes provides a theoretical basis for exploring the roles of AAAP family members in C. annuum.
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http://dx.doi.org/10.1186/s12864-021-07765-1DOI Listing
June 2021

A Retrospective, Observational Analysis of Tumor Infiltrating Lymphocytes and Tumor Regression in Melanoma.

J Surg Res 2021 Jun 18;267:203-208. Epub 2021 Jun 18.

Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA.

Background: Tumor infiltrating lymphocytes (TILs) and regression are thought to be distinct markers of the immune response to melanoma.

Objective: This study sought to analyze the relationship of TIL grade and presence of regression to each other and to other prognostic histopathologic and clinical values in melanoma.

Materials And Methods: A retrospective analysis was conducted using patients diagnosed with melanoma between 2013 and 2019 whose complete histopathologic reports were available.

Results: Regression was seen in 48.9%, 30.1% and 37.9% of patients with brisk, non-brisk, and absent TILs respectively (P=0.019). Melanoma tumors with brisk TILs were found to have a lower Breslow thickness than those with non-brisk or absent (P= 0.001). Tumors with regression were also found to have lower Breslow thickness (P<0.001). Neither TIL grade nor regression were protective of nodal metastasis or associated with improved survival.

Conclusion: Brisk TILs have a positive association with thinner tumors and the presence of tumor regression relative to non-brisk or absent TILs. This may suggest a more robust immune response in tumors with brisk TILs. Further exploration of the interplay between TIL grade, lymphocyte cell subtype and lymphocyte density may help explain this finding.
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http://dx.doi.org/10.1016/j.jss.2021.05.008DOI Listing
June 2021

Geniposide downregulates the VEGF/SphK1/S1P pathway and alleviates angiogenesis in rheumatoid arthritis in vivo and in vitro.

Phytother Res 2021 Jun 21. Epub 2021 Jun 21.

College of Pharmacy, Anhui University of Chinese Medicine, Hefei, China.

The VEGF/SphK1/S1P pathway is closely related to angiogenesis in rheumatoid arthritis (RA), but the precise underlying mechanisms are unclear at present. Here, we explored the involvement of the VEGF/SphK1/S1P cascade in RA models and determined the effects of GE intervention. Our results showed abnormal expression of proteins related to this pathway in RA synovial tissue. Treatment with GE effectively regulated the signal axis, inhibited angiogenesis, and alleviated RA symptoms. In vitro, TNF-ɑ enhanced the VEGF/SphK1/S1P pathway in a co-culture model of fibroblast-like synoviocytes (FLS) and vascular endothelial cells (VEC). GE induced downregulation of VEGF in FLS, restored the dynamic balance of pro-/antiangiogenic factors, and suppressed SphK1/S1P signaling in VEC, resulting in lower proliferation activity, migration ability, tube formation ability, and S1P secretion ability of VEC cells. Additionally, SphK1-specific small interfering RNA (siRNA) blocked the VEGF/SphK1/S1P cascade, which can effectively alleviate the stimulatory effect of FLS on VEC and further enhanced the therapeutic effect of GE. Taken together, our results demonstrate that GE suppresses the VEGF/SphK1/S1P pathway and alleviates the stimulation of VEC by FLS, thereby preventing angiogenesis and promoting therapeutic effects against RA.
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http://dx.doi.org/10.1002/ptr.7130DOI Listing
June 2021

Remodelin Is a Cryptic Assay Interference Chemotype That Does Not Inhibit NAT10-Dependent Cytidine Acetylation.

ACS Med Chem Lett 2021 Jun 27;12(6):887-892. Epub 2020 Jul 27.

Chemical Biology Laboratory, National Cancer Institute, Frederick, Maryland 21702, United States.

Remodelin is a putative small molecule inhibitor of the RNA acetyltransferase NAT10 which has shown preclinical efficacy in models of the premature aging disease Hutchinson-Gilford Progeria Syndrome (HGPS). Here we evaluate remodelin's assay interference characteristics and effects on NAT10-catalyzed RNA cytidine acetylation. We find the remodelin chemotype constitutes a cryptic assay interference compound, which does not react with small molecule thiols but demonstrates protein reactivity in ALARM NMR and proteome-wide affinity profiling assays. Biophysical analyses find no direct evidence for interaction of remodelin with the NAT10 acetyltransferase active site. Cellular studies verify that N4-acetylcytidine (ac4C) is a nonredundant target of NAT10 activity in human cell lines and find that this RNA modification is not affected by remodelin treatment in several orthogonal assays. These studies display the potential for remodelin's chemotype to interact with multiple protein targets in cells and indicate remodelin should not be applied as a specific chemical inhibitor of NAT10-catalyzed RNA acetylation.
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http://dx.doi.org/10.1021/acsmedchemlett.0c00193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201477PMC
June 2021

3D genome alterations associated with dysregulated HOXA13 expression in high-risk T-lineage acute lymphoblastic leukemia.

Nat Commun 2021 06 17;12(1):3708. Epub 2021 Jun 17.

The MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing, China.

3D genome alternations can dysregulate gene expression by rewiring enhancer-promoter interactions and lead to diseases. We report integrated analyses of 3D genome alterations and differential gene expressions in 18 newly diagnosed T-lineage acute lymphoblastic leukemia (T-ALL) patients and 4 healthy controls. 3D genome organizations at the levels of compartment, topologically associated domains and loop could hierarchically classify different subtypes of T-ALL according to T cell differentiation trajectory, similar to gene expressions-based classification. Thirty-four previously unrecognized translocations and 44 translocation-mediated neo-loops are mapped by Hi-C analysis. We find that neo-loops formed in the non-coding region of the genome could potentially regulate ectopic expressions of TLX3, TAL2 and HOXA transcription factors via enhancer hijacking. Importantly, both translocation-mediated neo-loops and NUP98-related fusions are associated with HOXA13 ectopic expressions. Patients with HOXA11-A13 expressions, but not other genes in the HOXA cluster, have immature immunophenotype and poor outcomes. Here, we highlight the potentially important roles of 3D genome alterations in the etiology and prognosis of T-ALL.
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http://dx.doi.org/10.1038/s41467-021-24044-5DOI Listing
June 2021

Combination of albumin-globulin score and skeletal muscle index predicts long-term outcomes of intrahepatic cholangiocarcinoma patients after curative resection.

Clin Nutr 2021 May 3;40(6):3891-3900. Epub 2021 May 3.

Department of Liver Surgery, Liver Transplantation Division, West China Hospital, Sichuan University, Chengdu, 610041, China; Laboratory of Liver Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China. Electronic address:

Background & Aims: Sarcopenia is characterized by loss of skeletal muscle mass and associated with poor postoperative outcomes. This study aimed to investigate the prognostic value of preoperative albumin-globulin score (AGS), skeletal muscle index (SMI) as well as their combination in patients with intrahepatic cholangiocarcinoma (ICC) treated with surgical resection.

Methods: A total of 613 newly diagnosed ICC patients from two centers were retrospectively analyzed (460 in discovery cohort and 153 in validation cohort). The plain computed tomography images were used to measure SMI. The effect of AGS, SMI and CAS grade on clinicopathological characteristics and long-term outcomes of patients with ICC were analyzed.

Results: The SMI was significantly greater in males than in females. Patients with decreased AGS, increased SMI were associated with improved overall survival (OS) and recurrence-free survival (RFS). Stratefied by CAS grade, 68 (14.8%) patients in grade 1 were associated with increased body mass index (BMI) and best postoperative prognosis, whereas 194 (42.1%) patients in grade 3 were linked to worst OS and RFS. The CAS grade showed a promising accuracy in predicting OS and RFS of ICC patients (area under curves [AUCs] were 0.732 and 0.768). Multiple tumors, MVI and elevated CAS grades were identified as independent risk factors for OS and RFS of ICC patients. These results were confirmed by validation cohort.

Conclusion: The present study provided compelling evidence that a novel index based on combination of preoperative AGS and SMI was closely related to postoperative long-term outcomes for surgically treated ICC patients. Preoperative evaluation of CAS grade may be useful for risk classification and clinical therapeutic decision-making for ICC patients.
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http://dx.doi.org/10.1016/j.clnu.2021.04.038DOI Listing
May 2021

Quantization Parameter Cascading for Surveillance Video Coding Considering All Inter Reference Frames.

IEEE Trans Image Process 2021 18;30:5692-5707. Epub 2021 Jun 18.

Video surveillance and its applications have become increasingly ubiquitous in modern daily life. In video surveillance system, video coding as a critical enabling technology determines the effective transmission and storage of surveillance videos. In order to meet the real-time or time-critical transmission requirements of video surveillance systems, the low-delay (LD) configuration of the advanced high efficiency video coding (HEVC) standard is usually used to encode surveillance videos. The coding efficiency of the LD configuration is closely related to the quantization parameter (QP) cascading technique which selects or determines the QPs for encoding. However, the quantization parameter cascading (QPC) technique currently adopted for the LD configuration in HEVC test model (i.e., HM) is not optimized since it has not taken full account of the reference dependency in coding. In this paper, an efficient QPC technique for surveillance video coding, referred to as QPC-SV, is proposed, considering all inter reference frames under the LD configuration. Experimental results demonstrate the efficacy of the proposed QPC-SV. Compared with the default configuration of QPC in the HM, the QPC-SV achieves significant rate-distortion performance gain with average BD-rates of -9.35% and -9.76% for the LDP and LDB configurations, respectively.
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http://dx.doi.org/10.1109/TIP.2021.3087413DOI Listing
June 2021

The SOX9-MMS22L Axis Promotes Oxaliplatin Resistance in Colorectal Cancer.

Front Mol Biosci 2021 27;8:646542. Epub 2021 May 27.

Department of Experimental Research, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China.

Background: Colorectal cancer (CRC) is estimated to be one of the most common cancers and the leading cause of cancer-related death worldwide. SOX9 is commonly overexpressed in CRC and participates in drug resistance. In addition, DNA damage repair confers resistance to anticancer drugs. However, the correlation between DNA damage repair and high SOX9 expression is still unclear. In this study, we aimed to investigate the function and the specific underlying mechanism of the SOX9-dependent DNA damage repair pathway in CRC.

Methods: The expression levels of SOX9 and MMS22L in CRC were examined by immunohistochemistry (IHC) and TCGA analysis. RNA sequencing was conducted in RKO SOX9-deficient cells and RKO shControl cells. Mechanistic studies were performed in CRC cells by modulating SOX9 and MMS22L expression, and we evaluated drug sensitivity and DNA damage repair signaling events. In addition, we investigated the effect of oxaliplatin in tumors with SOX9 overexpression and low expression of MMS22L .

Results: Our study showed that SOX9 has a higher expression level in CRC tissues than in normal tissues and predicts poor prognosis in CRC patients. Overexpression and knockdown of SOX9 were associated with the efficacy of oxaliplatin. In addition, SOX9 activity was enriched in the DNA damage repair pathway regulation of MMS22L expression and participation in DNA double-strand break repair. SOX9 was upregulated and formed a complex with MMS22L, which promoted the nuclear translocation of MMS22L upon oxaliplatin treatment. Moreover, the enograft assay results showed that oxaliplatin abrogated tumor growth from cells with MMS22L downregulation in mice.

Conclusions: In CRC, activation of the SOX9-MMS22L-dependent DNA damage pathway is a core pathway regulating oxaliplatin sensitivity. Targeting this pathway in oxaliplatin-resistant CRC cells is a promising therapeutic option.
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http://dx.doi.org/10.3389/fmolb.2021.646542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191464PMC
May 2021

Liver Transplantation Liver Resection for Stage I and II Hepatocellular Carcinoma: Results of an Instrumental Variable Analysis.

Front Oncol 2021 26;11:592835. Epub 2021 May 26.

Department of Plastic and Burns Surgery, West China Hospital, Sichuan University, Chengdu, China.

Background: This study aimed to compare the long-term outcomes of liver transplantation (LT) and liver resection (LR) among patients with stage I and II hepatocellular carcinoma (HCC).

Methods: SEER 18 registry from 2004 to 2015 was retrieved for this study. We included 1,765 and 1,746 cases with stage I-II (AJCC, 7) HCC in the multivariable analyses and instrumental variable (IV) analyses, respectively. Propensity score matching (PSM) was further carried out to ensure comparability. Propensity score to receive LT was adjusted by stabilized inverse probability of treatment weighting (IPTW) and standardized mortality ratio weighting (SMRW) methods. In addition, IV analysis was performed to adjust both measured and unmeasured confounding factors.

Results: We identified 1,000 (56.7%) and 765 (43.3%) patients treated with LR and LT, respectively. In the multivariable adjusted cohort, after adjusting potential confounders, patients undergoing LT offered significant prognostic advantages over LR in overall survival (OS, P < 0.001) and disease-free survival (DSS, P < 0.001). The instrument variable in this study is LT rates in various Health Service Areas (HSAs). Results from the IV analysis showed that cases treated with LT had significantly longer OS (P = 0.001) and DSS (P < 0.001). In IV analysis stratified by clinicopathologic variables, the treatment effect of LT LR in OS was consistent across all subgroups. Regarding DSS in IV analyses, the subgroup analyses observed that LT had better DSS across all subgroups, except for similar results in the older patients (interaction P value = 0.039) and the non-White patients (interaction P value = 0.041). In the propensity-matched cohort, patients with LT still had better OS (P < 0.001) and DSS (P < 0.001) in comparison to cases who underwent LR. In both IPTW and SMRW cohorts, patients who underwent LT had better OS (both P values < 0.001) and DSS (both P values < 0.001).

Conclusions: LT provided a survival benefit for cases with stage I-II HCC. These results indicated that if LT rate was to increase in the future, average long-term survival may also increase. However, for some special populations such as the elderly patients, owing to the similar outcomes between LT and LR, the selection of LT should be cautious.
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http://dx.doi.org/10.3389/fonc.2021.592835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189150PMC
May 2021

Ion-molecule reactions catalyzed by a single gold atom.

Chem Sci 2020 Jul 27;11(32):8502-8505. Epub 2020 Jul 27.

Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China Hefei 230026 P. R. China

We report that Au atoms within van der Waals complexes serve as catalysts for the first time. This was observed in ionization-induced chemistry of 1,6-hexanediol-Au and 1,8-octanediol-Au complexes formed in superfluid helium nanodroplets, where the addition of Au atom(s) made CH the sole prominent product in dissociative reactions. Density functional theory (DFT) calculations showed that the Au atom significantly strengthens all of the C-C bonds and weakens the C-O bonds in the meantime, making the C-C bonds stronger than the two C-O bonds in the ionized complexes. This leads to a preferential cleavage of the C-O bonds and thus a strong catalytic effect of the Au atoms in the reactions.
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http://dx.doi.org/10.1039/d0sc03523hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163403PMC
July 2020

Peritumoral Tertiary Lymphoid Structures Correlate With Protective Immunity and Improved Prognosis in Patients With Hepatocellular Carcinoma.

Front Immunol 2021 26;12:648812. Epub 2021 May 26.

Department of Liver Surgery, Liver Transplantation Division, West China Hospital, Sichuan University, Chengdu, China.

The existence of intratumoral tertiary lymphoid structure (iTLS) has been reported to correlative with favorable clinical outcomes for patients with hepatocellular carcinoma (HCC). However, little is known about the role of peritumoral TLS (pTLS). This study aimed to investigate the prognostic role of pTLS either alone or jointly with iTLS and the potential association with local immune response in HCC. The formation and cellular composition of TLS was evaluated by hematoxylin & eosin and immunohistochemistry. Evaluation of tumor-infiltrating immune cells and formation of germinal center (GC) inside TLS was performed by immunohistochemistry. The gene expression profiles were analyzed by real-time PCR. In a total of 360 patients from two independent cohorts, the pTLS was identified in most, whereas iTLS could be observed in only approximately 30% of HCC specimens. Patients with high pTLS densities were associated with improved outcomes, those present with characteristic morphology of GC, particularly, showing an even better prognosis. The combination of pTLS and iTLS allowed the identification of patients with best prognosis. Tumors with high pTLS density showed significantly increased expression of Th1-, Th17- and immune suppression-related genes, as well as significantly higher infiltration of CD3+, CD8+ and CD20+ cells and lower infiltration of FOXP3+, CD68+ and PD1+ cells. Conclusively, we provide evidence that pTLS is associated with intratumoral immune infiltration, highlighting the dynamic interplay between pTLS and immune cells recruitment. High pTLS density links to a tumor microenvironment with an active immune reaction and improved patient survival and represents a promising prognostic biomarker for HCC.
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http://dx.doi.org/10.3389/fimmu.2021.648812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187907PMC
May 2021

Comparison of the efficacy of thoracoscopic simultaneous resection of bullae via transxiphoid process and intercostal approach.

Asian J Surg 2021 Jun 9. Epub 2021 Jun 9.

Department of Third Surgical, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, 445000, China. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2021.04.014DOI Listing
June 2021

Near-Infrared Spectroscopy Monitoring of Cerebral Oxygenation and Influencing Factors in Neonates from High-Altitude Areas.

Neonatology 2021 Jun 9:1-6. Epub 2021 Jun 9.

Pediatric Department, Peking University First Hospital, Beijing, China.

Background: Accurate detection of cerebral oxygen saturation (rSO2) may be useful for neonatal brain injury prevention, and the normal range of rSO2 of neonates at high altitude remained unclear.

Objective: To compare cerebral rSO2 and cerebral fractional tissue oxygen extraction (cFTOE) at high-altitude and low-altitude areas in healthy neonates and neonates with underlying diseases.

Methods: 515 neonates from low-altitude areas and 151 from Tibet were enrolled. These neonates were assigned into the normal group, hypoxic-ischemic encephalopathy (HIE) group, and other diseases group. Near-infrared spectroscopy was used to measure rSO2 in neonates within 24 h after admission. The differences of rSO2, pulse oxygen saturation (SpO2), and cFTOE levels were compared between neonates from low- and high-altitude areas.

Results: (1) The mean rSO2 and cFTOE levels in normal neonates from Tibet were 55.0 ± 6.4% and 32.6 ± 8.5%, significantly lower than those from low-altitude areas (p < 0.05). (2) At high altitude, neonates with HIE, pneumonia (p < 0.05), anemia, and congenital heart disease (p < 0.05) have higher cFTOE than healthy neonates. (3) Compared with HIE neonates from plain areas, neonates with HIE at higher altitude had lower cFTOE (p < 0.05), while neonates with heart disease in plateau areas had higher cFTOE than those in plain areas (p < 0.05).

Conclusions: The rSO2 and cFTOE levels in normal neonates from high-altitude areas are lower than neonates from the low-altitude areas. Lower cFTOE is possibly because of an increase in blood flow to the brain, and this may be adversely affected by disease states which may increase the risk of brain injury.
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http://dx.doi.org/10.1159/000514403DOI Listing
June 2021

The Value of Blood Urea Nitrogen in the Prediction of Risks of Cardiovascular Disease in an Older Population.

Front Cardiovasc Med 2021 20;8:614117. Epub 2021 May 20.

Shanghai East Hospital, Tongji University, Shanghai, China.

High blood urea nitrogen (BUN) is associated with adverse outcomes in patients with cardiac disease risks. However, no study has explored whether BUN can predict the risk of cardiovascular disease (CVD) in the healthy older population. This study aims to explore the incidence and risk factors of CVD among a healthy older population community in China. This study was designed as a cohort study with a 4-year follow-up. We recruited 5,000 older people among 137,625 residents of the Gaohang community. In the baseline, subjects were asked to participate in medical screening and biological tests, and answered survey questions. During the follow-up period (2014-2017), the researchers regularly tested the subjects' indicators and assessment scales. We monitored the occurrence of CVD and explored the relationship between BUN and CVD via a Cox regression analysis. During the follow-up, subjects were newly diagnosed with CVD including heart failure (HF), heart disease events, atrial fibrillation, diabetes, hypertension, metabolic syndrome, and kidney disease. The Cox regression analysis found an association between baseline BUN and incident CVD in female subjects, with higher BUN associated with increased risk of AF in females and kidney disease in both male and females. No association was found between BUN and CVD in male subjects. Current results indicate that BUN is a valuable predictive biomarker of CVD. A higher BUN level (>13.51 mg/dL) is associated with an increased occurrence of HF but a decreased occurrence of diabetes and metabolic symptoms in normal older females.
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http://dx.doi.org/10.3389/fcvm.2021.614117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173137PMC
May 2021

Gold-iron selenide nanocomposites for amplified tumor oxidative stress-augmented photo-radiotherapy.

Biomater Sci 2021 Jun;9(11):3979-3988

Key Laboratory of Advanced Materials, Ministry of Education of China, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China. and State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China.

The radio-resistance of tumor tissues has been considered a great challenge for cancer radiotherapy (RT).The development of nanoparticle (NP)-based radio-sensitizers can enhance the radio-sensitization of tumor tissues while reducing the side effects to surrounding tissues. However, most of the nano-radiosensitizers show increased radiation deposition with a high-Z element but achieve limited enhancement. Herein, we investigated polyethylene glycol (PEG)-modified gold-iron selenide nanocomposites (Au-FeSe2 NCs) for simultaneously enhancing therapeutic effects in multiple ways. In this study, the high-Z element Au (Z = 79) endows Au-FeSe2 NCs with enhanced X-ray deposition and thus causes more DNA damage. On the other hand, Au-FeSe2 exhibits the ability to produce reactive oxygen species (ROS) by catalyzing endogenous hydrogen peroxide in tumor sites as well as improve the hydrogen peroxide level during ionizing irradiation. Finally, combined with photothermal therapy (PTT), Au-FeSe2 NCs could exhibit a remarkable RT/PTT synergistic effect on tumor treatment.
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http://dx.doi.org/10.1039/d1bm00306bDOI Listing
June 2021

Tight covalent organic framework membranes for efficient anion transport via molecular precursor engineering.

Angew Chem Int Ed Engl 2021 Jun 1. Epub 2021 Jun 1.

Tianjin University, School of Chemical Engineering and Technology, Weijin Road, 300072, Tianjin, CHINA.

Fabricating covalent organic frameworks (COFs) membranes with tight structure, which can fully utilize well-defined framework structure and thus achieve superior conduction performance, remains a grand challenge. Herein, through molecular precursor engineering of COFs, we reported the fabrication of tight COFs membrane with the ever-reported highest hydroxide ion conductivity over 200 mS cm-1 at 80 °C, 100% RH. Six quaternary ammonium-functionalized COFs were synthesized by assembling functional hydrazides and different aldehyde precursors. In an organic-aqueous reaction system, the impact of the aldehyde precursors with different size, electrophilicity and hydrophilicity on the reaction-diffusion process for fabricating COFs membranes was elucidated. Particularly, more hydrophilic aldehydes were prone to push the reaction zone from the interface region to the aqueous phase of the reaction system, the tight membranes were thus fabricated via phase-transfer polymerization process, conferring around 4~8 times the anion conductivity over the loose membranes via interfacial polymerization process.
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http://dx.doi.org/10.1002/anie.202105190DOI Listing
June 2021

Scalable fabrication of crystalline COF membrane from amorphous polymeric membrane.

Angew Chem Int Ed Engl 2021 Jun 1. Epub 2021 Jun 1.

Tianjin University, School of Chemical Engineering and Technology, Weijin Road, 300072, Tianjin, CHINA.

Covalent organic framework (COF) membranes hold tremendous potential for widespread applicability, but their scalable fabrication remains challenging. Here, we demonstrate the disorder-to-order transformation from amorphous polymeric membrane to crystalline COF membrane via monomer exchange. Solution-processing method is used to prepare amorphous membranes and the replacing monomer is selected based on the chemical and thermodynamical stability of the final framework. Afterwards, the reversible imine bonds allow the extraneous monomers to replace the pristine monomers within amorphous membrane, driving the transformation from disordered network to ordered framework. The incorporation of intramolecular hydrogen bonds enables the crystalline COF to imprint the morphology of amorphous membrane. The COF membranes harvest proton conductivity up to 0.53 S cm -1 at 80 °C. Our strategy builds a bridge between amorphous polymeric and crystalline COF membranes, not only paving the way to large-scale fabrication of COF membranes, but also affording some guidance on materials processing via disorder-to-order transformation.
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http://dx.doi.org/10.1002/anie.202102965DOI Listing
June 2021

A Guideline-Based Decision Tree Achieves Better Glucose Control with Less Hypoglycemia at 3 Months in Chinese Diabetic Patients.

Diabetes Ther 2021 05 29. Epub 2021 May 29.

Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China.

Introduction: China has the world's largest diabetes epidemic and has been facing a serious shortage of primary care providers for chronic diseases including diabetes. To help primary care physicians follow guidelines and mitigate the workload in primary care communities in China, we developed a guideline-based decision tree. This study aimed to validate it at 3 months with real-world data.

Methods: The decision tree was developed based on the 2017 Chinese Type 2 Diabetes (T2DM) guideline and 2018 guideline for primary care. It was validated with the data from two registry studies: the NEW2D and ORBIT studies. Patients' data were divided into two groups: the compliance and non-compliance group, depending on whether the physician's prescription was consistent with the decision tree or not. The primary outcome was the difference of change in HbA1c from baseline to 3 months between the two groups. The secondary outcomes included the difference in the proportion of patients achieving HbA1c < 7% at 3 months between the two groups, the incidence of self-reported hypoglycemia at 3 months, and the proportion of patients (baseline HbA1c ≥ 7%) with a HbA1c reduction ≥ 0.3%. The statistical analysis was performed using linear or logistic regression with inverse probability of treatment weighting with adjustments of confounding factors.

Results: There was a 0.9% reduction of HbA1c in the compliance group and a 0.8% reduction in the non-compliance group (P < 0.001); 61.1% of the participants in the compliance group and 44.3% of the participants in the non-compliance group achieved a HbA1c level < 7% at 3 months (P < 0.001). The hypoglycemic events occurred in 7.1% of patients in the compliance group vs. 9.4% in the non-compliance group (P < 0.001).

Conclusion: The decision tree can help physicians to treat their patients so that they achieve their glycemic targets with fewer hypoglycemic risks. ( http://www.clinicaltrials.gov NCT01525693 & NCT01859598).
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http://dx.doi.org/10.1007/s13300-021-01075-1DOI Listing
May 2021

Successful management of the hepatocellular carcinoma with inferior vena cava tumor thrombus: A case report.

Medicine (Baltimore) 2021 May;100(21):e26081

Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy.

Rationale: Hepatocellular carcinoma (HCC) with inferior vena cava tumor thrombus (IVCTT) is traditionally considered an advanced-stage cancer with a poor prognosis. There is no standard treatment for patients diagnosed as HCC with IVCTT.

Patient Concerns: A 52-year-old man was admitted to our hospital because of suspected hepatic mass during a health examination.

Diagnoses: Computed tomography (CT) showed a hepatic mass approximately 4.3 cm × 6.3 cm in size located in segment VII of the liver, with thrombus in the inferior vena cava. The mass exhibited a pattern of early enhancement and washout on contrast-enhanced CT. Alpha-fetoprotein was 614.1 ng/mL (normal value, <8 ng/mL). The preoperative diagnosis was HCC with IVCTT.

Interventions: Two months after stereotactic body radiotherapy combined with sorafenib therapy, a planned open anatomical resection of the right posterior lobe of the liver was performed.

Outcomes: The patient is alive without disease 12 months after surgery, and the level of alpha-fetoprotein is normal.

Lessons: The patient diagnosed as HCC with IVCTT was successfully treated by stereotactic body radiotherapy combined with molecularly targeted drugs followed by surgical treatment. If confirmed in future studies, this would suggest a promising strategy for the management of HCC with IVCTT.
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http://dx.doi.org/10.1097/MD.0000000000026081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154412PMC
May 2021

The response of macrophages and their osteogenic potential modulated by micro/nano-structured Ti surfaces.

Colloids Surf B Biointerfaces 2021 May 13;205:111848. Epub 2021 May 13.

State Key Laboratory of Powder Metallurgy, Central South University, Changsha, 410083, PR China. Electronic address:

Current understanding on the interactions between micro/nano-structured Ti surfaces and macrophages is still limited. In this work, TiO nano-structures were introduced onto acid-etched Ti surfaces by alkali-heat treatment, ion exchange and subsequent heat treatment. By adjusting the concentration of NaOH during alkali-heat treatment, nano-flakes, nano-flakes mixed with nano-wires or nano-wires could formed on acid-etched Ti surfaces. The micro- and micro/nano-structured Ti surfaces possessed similar surface chemical and phase compositions. In vitro results indicate that the morphology of macrophages was highly dependent on the morphological features of nano-structures. Nano-flakes and nano-wires were favorable to induce the formation of lamellipodia and filopodia, respectively. Compared to micro-structured Ti surface, micro/nano-structured Ti surfaces polarized macrophages to their M2 phenotype and enhanced the gene expressions of osteogenic growth factors in macrophages. The M2 polarized macrophages promoted the maturation of osteoblasts. Compared to that with nano-flakes or nano-wires, the surface with mixed features of nano-flakes and nano-wires exhibited stronger anti-inflammatory and osteo-immunomodulatory effects. The findings presented in the current work suggest that introducing micro/nano-topographies onto Ti-based implant surfaces is a promising strategy to modulate the inflammatory response and mediate osteogenesis.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111848DOI Listing
May 2021

The Transcriptomic Landscape of Mismatch Repair-Deficient Intestinal Stem Cells.

Cancer Res 2021 May 18;81(10):2760-2773. Epub 2021 Mar 18.

Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Lynch syndrome is the most common cause of hereditary colorectal cancer and is secondary to germline alterations in one of four DNA mismatch repair (MMR) genes. Here we aimed to provide novel insights into the initiation of MMR-deficient (MMRd) colorectal carcinogenesis by characterizing the expression profile of MMRd intestinal stem cells (ISC). A tissue-specific MMRd mouse model (Villin-Cre;Msh2 ) was crossed with a reporter mouse () to trace and isolate ISCs (Lgr5+) using flow cytometry. Three different ISC genotypes (-KO, -HET, and -WT) were isolated and processed for mRNA-seq and mass spectrometry, followed by bioinformatic analyses to identify expression signatures of complete MMRd and haplo-insufficiency. These findings were validated using qRT-PCR, IHC, and whole transcriptomic sequencing in mouse tissues, organoids, and a cohort of human samples, including normal colorectal mucosa, premalignant lesions, and early-stage colorectal cancers from patients with Lynch syndrome and patients with familial adenomatous polyposis (FAP) as controls. -KO ISCs clustered together with differentiated intestinal epithelial cells from all genotypes. Gene-set enrichment analysis indicated inhibition of replication, cell-cycle progression, and the Wnt pathway and activation of epithelial signaling and immune reaction. An expression signature derived from MMRd ISCs successfully distinguished MMRd neoplastic lesions of patients with Lynch syndrome from FAP controls. SPP1 was specifically upregulated in MMRd ISCs and colocalized with LGR5 in Lynch syndrome colorectal premalignant lesions and tumors. These results show that expression signatures of MMRd ISC recapitulate the initial steps of Lynch syndrome carcinogenesis and have the potential to unveil novel biomarkers of early cancer initiation. SIGNIFICANCE: The transcriptomic and proteomic profile of MMR-deficient intestinal stem cells displays a unique set of genes with potential roles as biomarkers of cancer initiation and early progression.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-2896DOI Listing
May 2021

Analysis of the influencing factors and nursing strategy for acute atelectasis after traumatic brain injury surgery.

Ann Palliat Med 2021 May 10;10(5):5425-5432. Epub 2021 May 10.

Department of Neurosurgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Background: Acute atelectasis is common after traumatic brain injury (TBI), but the related factors and treatment are still unclear. This study is to analyze the independent risk factors for acute atelectasis after TBI and propose an interventional nursing strategy, in order to correct respiratory function and improve the prognosis of patients.

Methods: The clinical data of 93 patients with TBI admitted to our hospital from April 2015 to October 2019 were retrospectively analyzed. Clinical data were analyzed by single factor analysis, the cutoff value of influencing factors was obtained by receiver operating characteristic (ROC) curve analysis, and the influencing factors for acute atelectasis after TBI were examined by multi-factor logistic regression.

Results: Twenty-two patients (23.66%) were complicated with acute atelectasis during the observation period, while the remaining 71 patients (76.34%) did not have acute atelectasis. Univariate analysis showed that there were significant differences in the Glasgow Coma Scale (GCS), history of vomiting and aspiration, mannitol use, mechanical ventilation, hypoalbuminemia, and serum hypoxia-inducible factor-1α (HIF-1α) between the acute atelectasis group and the non-acute atelectasis group (P<0.05). The AUC area of HIF-1α level predicting acute atelectasis was 0.896 [95% confidence interval (CI): 0.814-0.978, P=0.042], and the cut-off value was 2.12 mmol/L, with a sensitivity of 76.9% and a specificity of 93.3%. Logistic regression analysis showed that a history of vomiting and aspiration [odds ratio (OR) 3.908, 95% confidence interval (CI): 1.201-12.712], mechanical ventilation (OR 3.250, 95% CI: 1.139-9.271), hypoalbuminemia (OR 5.741, 95% Cl: 1.926-17.113), and HIF-1α ≥2.12 mmol/L (OR 6.623, 95% CI: 2.364-16.346) were independent risk factors for acute atelectasis after TBI.

Conclusions: A history of vomiting and aspiration, mechanical ventilation, hypoalbuminemia, and high expression of HIF-1α are all independent risk factors for postoperative acute atelectasis in patients with TBI. In clinical practice, patients should be guided to swallow properly, breathe smoothly, eat well, and regularly check the relevant indexes.
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http://dx.doi.org/10.21037/apm-21-790DOI Listing
May 2021

Gene expression signatures differentiating major depressive disorder from subsyndromal symptomatic depression.

Aging (Albany NY) 2021 05 8;13(9):13124-13137. Epub 2021 May 8.

Clinical Research Center, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.

Subsyndromal symptomatic depression (SSD) and major depressive disorder (MDD) have been classified as distinct diseases, due to their dissimilar gene expression profiles and responses to venlafaxine. To identify specific biomarkers of these two diseases, we conducted a secondary analysis of the gene expression signatures of SSD patients, MDD patients and healthy controls (n=8/group) from the study of Yi et al. Global, individual, specific, enrichment and co-expression analyses were used to compare the transcriptomic profiles of peripheral blood lymphocytes from the three groups. The global and individual analyses revealed that different genes were up- and downregulated in the SSD and MDD groups. Through our specific analysis, we identified 1719 and 3278 differentially expressed genes specifically associated with MDD and SSD, respectively. Enrichment and co-expression analyses demonstrated that the genes specific to MDD were enriched in pathways associated with hormone levels and immune responses, while those specific to SSD were associated with immune function. The specific hub gene for the MDD co-expression network was transmembrane protein 132B (TMEM132B), while the hub genes for SSD were actin-related protein 2/3 complex (ARPC2) and solute carrier family 5 member 5 (SLC5A5). This bioinformatic analysis has provided potential biomarkers that can distinguish SSD from MDD.
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http://dx.doi.org/10.18632/aging.202995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148500PMC
May 2021

Optimizing the sulfonic groups of a polymer to coat the zinc anode for dendrite suppression.

Chem Commun (Camb) 2021 May;57(43):5326-5329

School of Advanced Materials, Peking University Shenzhen Graduate School, Shenzhen 518055, P. R. China.

The zinc metal anodes in aqueous zinc-ion batteries suffer from low cycling performance caused by uncontrolled dendrite. We have designed sulfonated poly-ether-ether-ketone (SPEEK) polymers as a surface coating layer on the zinc anode for dendrite suppression, in which the sulfonic groups in polymers act as effective active sites for zinc-ion diffusion. In SPEEK, the un-sulfonated domain serves as the framework and the sulfonated domain serves as the functional part to re-distribute the zinc ions. By optimizing the degree of SPEEK sulfonation, the best zinc anode coating has been achieved to present a high reversibility of over 1600 hours in symmetric cells and improved performance in full cells.
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http://dx.doi.org/10.1039/d1cc00924aDOI Listing
May 2021

Fabrication of Nano/Micro-Structured Electrospun Detection Card for the Detection of Pesticide Residues.

Foods 2021 Apr 19;10(4). Epub 2021 Apr 19.

College of Biosciences and Bioengineering, South China University of Technology, Guangzhou 510640, China.

A novel nano/micro-structured pesticide detection card was developed by combining electrospinning and hydrophilic modification, and its feasibility for detecting different pesticides was investigated. Here, the plain and hydrophilic-modified poly(ε-caprolactone) (PCL) fiber mats were used for the absorption of indolyl acetate and acetylcholinesterase (AChE), respectively. By pre-treating the fiber mat with ethanol, its surface wettability was improved, thus, promoting the hydrolysis of the PCL fiber mat. Furthermore, the absorption efficiency of AChE was improved by almost two times due to the increased hydrophilicity of the modified fiber mat. Noteworthily, this self-made detection card showed a 5-fold, 2-fold, and 1.5-fold reduction of the minimum detectable concentration for carbofuran, malathion, and trichlorfon, respectively, compared to the national standard values. Additionally, it also exhibited good stability when stored at 4 °C and room temperature. The food detection test showed that this nano/micro-based detection card had better detectability than the commercial detection card. Therefore, this study offers new insights into the design of pesticide detection cards, which also broadens the application of electrospinning technique.
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http://dx.doi.org/10.3390/foods10040889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073816PMC
April 2021

Tannic acid-based metal phenolic networks for bio-applications: a review.

J Mater Chem B 2021 05;9(20):4098-4110

Key Laboratory of Advanced Materials, Ministry of Education of China, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China. and State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China.

Tannic acid (TA), a large polyphenolic molecule, has long been known for use in food additives, antioxidants, bio-sorbents, animal feed and adhesives due to its intrinsic properties such as antioxidation, metal chelation, and polymerization. Recently, there has been a renewed interest in fabricating engineered advanced materials with TA modification for novel bio-applications. The modification process involves various interactions/reactions based on its diverse chemical structure, contributed by abundant aromatic rings and hydroxyl groups. In addition, the obtained composites are endowed with retained TA activity and novel enhanced properties. Therefore, the aim of this review is to highlight the recent biomedical application of TA-based metal phenolic networks (TA-MPNs) by focusing on their intrinsic properties and the endowed ability for novel engineered functional composites. The potential contributions of TA-MPNs in "Tumor Theranostics", "Anti-Bacterial Ability", "Wound Repair for Skin Regeneration" and "Bone Tissue Regeneration Applications" are summarized in this paper.
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http://dx.doi.org/10.1039/d1tb00383fDOI Listing
May 2021

MiR-326 mediates malignant biological behaviors of lung adenocarcinoma by targeting ZEB1.

Sci Prog 2021 Apr-Jun;104(2):368504211009379

School of medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.

MiR-326 functions as an antioncogene in the several types of cancer. However, the underling mechanisms through which miRNA-326 regulates the anti-carcinogenesis of lung adenocarcinoma have remained elusive. The aim of this study was to explore the role and regulatory mechanism of miR-326 in cell proliferation, invasion, migration and apoptosis in lung adenocarcinoma. Quantitative real-time PCR (qRT-PCR) was used to detect the expression pattern of miR-326 in human bronchial epithelial cells (HBES-2B), 4 kinds of lung adenocarcinoma cell lines (H23, H1975, H2228, H2085) and 20 lung adenocarcinoma tissues. Then, H23 cells were infected with miR-326 mimics, miR-326 inhibitors and si-ZEB1 to build up-regulated miR-326 cell lines, down-regulated ZEB1(zinc-finger-enhancer binding protein 1)cell lines, simultaneous down-regulated ZEB1 and miR-326 cell lines. Moreover, CCK-8 assay, transwell invasion assay, wound healing assay and flow cytometry assay were employed to examine the effects of miR-326 and ZEB1 on the proliferation, invasion, migration and apoptosis abilities of H23 cells. Western blot was performed to explore the effects of miR-326 and ZEB1 on the expression of invasion and migration related proteins N-cadherin, E-cadherin, MMP7, MMP13, SLUG and apoptotic proteins PARP, BAX. On the mechanism, a dual-luciferase reporter gene was used to measure the target relationship between miR-326 and ZEB1. MiR-326 expression was significantly downregulated in lung adenocarcinoma tissues and cells. Overexpression of miR-326 significantly inhibited the malignant behaviors of H23 cells. Mechanically, luciferase reporter assay showed that ZEB1 was a direct target of miR-326. MiR-326 mimic downregulated the expression of ZEB1. Furthermore, knocking down ZEB1 strongly inhibited the proliferation, invasion and migration of H23 cells but promoted apoptosis. MiR-326 could target ZEB1 to inhibit the proliferation, invasion and migration of lung adenocarcinoma cells and promote apoptosis, which is a potential therapeutic target for lung adenocarcinoma.
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http://dx.doi.org/10.1177/00368504211009379DOI Listing
April 2021

The role of transcriptomic biomarkers of endometrial receptivity in personalized embryo transfer for patients with repeated implantation failure.

J Transl Med 2021 04 28;19(1):176. Epub 2021 Apr 28.

Department of Reproductive Medicine, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410000, Hunan, China.

Background: Window of implantation (WOI) displacement is one of the endometrial origins of embryo implantation failure, especially repeated implantation failure (RIF). An accurate prediction tool for endometrial receptivity (ER) is extraordinarily needed to precisely guide successful embryo implantation. We aimed to establish an RNA-Seq-based endometrial receptivity test (rsERT) tool using transcriptomic biomarkers and to evaluate the benefit of personalized embryo transfer (pET) guided by this tool in patients with RIF.

Methods: This was a two-phase strategy comprising tool establishment with retrospective data and benefit evaluation with a prospective, nonrandomized controlled trial. In the first phase, rsERT was established by sequencing and analyzing the RNA of endometrial tissues from 50 IVF patients with normal WOI timing. In the second phase, 142 patients with RIF were recruited and grouped by patient self-selection (experimental group, n = 56; control group, n = 86). pET guided by rsERT was performed in the experimental group and conventional ET in the control group.

Results: The rsERT, comprising 175 biomarker genes, showed an average accuracy of 98.4% by using tenfold cross-validation. The intrauterine pregnancy rate (IPR) of the experimental group (50.0%) was significantly improved compared to that (23.7%) of the control group (RR, 2.107; 95% CI 1.159 to 3.830; P = 0.017) when transferring day-3 embryos. Although not significantly different, the IPR of the experimental group (63.6%) was still 20 percentage points higher than that (40.7%) of the control group (RR, 1.562; 95% CI 0.898 to 2.718; P = 0.111) when transferring blastocysts.

Conclusions: The rsERT was developed to accurately predict the WOI period and significantly improve the pregnancy outcomes of patients with RIF, indicating the clinical potential of rsERT-guided pET. Trial registration Chinese Clinical Trial Registry: ChiCTR-DDD-17013375. Registered 14 November 2017, http://www.chictr.org.cn/index.aspx.
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http://dx.doi.org/10.1186/s12967-021-02837-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082865PMC
April 2021

The SiTian Project.

An Acad Bras Cienc 2021 23;93(suppl 1):e20200628. Epub 2021 Apr 23.

National Astronomical Observatories, Chinese Academy of Sciences, 20A Datun Rd, Chaoyang 100101, Beijing, China.

SiTian is an ambitious ground-based all-sky optical monitoring project, developed by the Chinese Academy of Sciences. The concept is an integrated network of dozens of 1-m-class telescopes deployed partly in China and partly at various other sites around the world. The main science goals are the detection, identification and monitoring of optical transients (such as gravitational wave events, fast radio bursts, supernovae) on the largely unknown timescales of less than 1 day; SiTian will also provide a treasure trove of data for studies of AGN, quasars, variable stars, planets, asteroids, and microlensing events. To achieve those goals, SiTian will scan at least 10,000 square deg of sky every 30 min, down to a detection limit of $V \approx 21$ mag. The scans will produce simultaneous light-curves in 3 optical bands. In addition, SiTian will include at least three 4-m telescopes specifically allocated for follow-up spectroscopy of the most interesting targets. We plan to complete the installation of 72 telescopes by 2030 and start full scientific operations in 2032.
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http://dx.doi.org/10.1590/0001-3765202120200628DOI Listing
April 2021

Prediction of Prognosis for cHCC-CC Patients After Surgery: Comparison of Tumor Marker Score Based on AFP, CEA, CA19-9, and Other Clinical Stages.

Ann Surg Oncol 2021 Apr 26. Epub 2021 Apr 26.

Department of Liver Surgery and Liver Transplantation Center, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Background: The effectiveness of clinical stage as a prognostic factor in combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) patients is controversial.

Patients And Methods: Medical records of all pathologically confirmed cHCC-CC patients from 2000 to 2017 at West China Hospital were retrieved. Tumor marker score (TMS) was determined from optimal AFP, CEA, and CA19-9 cutoff values. Interaction and subgroup analysis were conducted according to potential confounders. Prognostic value of TMS and other prognostic models were evaluated by Kaplan-Meier (K-M) analysis, c-index, and time-dependent receiver operating curves (td-ROC).

Results: Optimal cutoff values for preoperative AFP, CEA, and CA19-9 were 10.76 ng/mL, 5.24 ng/mL, and 31.54 U/mL, respectively. Among 128 patients, 24, 58, and 46 were classified into TMS 0, TMS 1, and TMS ≥ 2, respectively. TMS could stratify our series into groups of statistically different prognosis. Subgroup analysis according to potential confounders and test for interactions showed that TMS 1 and TMS ≥ 2 were stable risk factors relative to TMS 0. Univariate (HR: TMS1 = 2.30, p = 0.014; TMS ≥ 2 = 5.1, p < 0.001) and multivariate Cox regression analyses (HR: TMS1 = 1.72, p = 0.124; TMS ≥ 2 = 4.15, p < 0.001) identified TMS as an independent prognostic risk factor. TMS had good discrimination (c-index 0.666, 95% CI 0.619-0.714), and calibration plots revealed favorable consistency. Area under the curve (AUC) value of td-ROC for TMS and integrated AUC was higher than for other clinical stages at any month within 5 years postoperation.

Conclusion: TMS exhibited optimal prognostic value over other widely used clinical stages for cHCC-CC after surgery and may guide clinicians in prognostic prediction.
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http://dx.doi.org/10.1245/s10434-021-09949-1DOI Listing
April 2021